miRNA screening reveals a new miRNA family stimulating iPS cell generation via regulation of Meox2

被引:72
作者
Pfaff, Nils [2 ]
Fiedler, Jan [3 ]
Holzmann, Angelika [3 ]
Schambach, Axel [4 ,5 ]
Moritz, Thomas [2 ]
Cantz, Tobias [1 ]
Thum, Thomas [3 ,6 ]
机构
[1] Hannover Med Sch, REBIRTH Grp Stem Cell Biol, D-30625 Hannover, Germany
[2] Hannover Med Sch, REBIRTH Grp Reprogramming, D-30625 Hannover, Germany
[3] Hannover Med Sch, Inst Mol & Translat Therapeut Strategies, IFB Tx, D-30625 Hannover, Germany
[4] Hannover Med Sch, REBIRTH Grp Hematopoiet Cell Therapy, D-30625 Hannover, Germany
[5] Hannover Med Sch, Dept Expt Hematol, D-30625 Hannover, Germany
[6] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy
关键词
induced pluripotent stem cells; Meox2; miRNAs; reprogramming; STEM-CELLS; MOUSE; GAX; GENE; ANGIOGENESIS; EXPRESSION;
D O I
10.1038/embor.2011.176
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Induced pluripotent stem cells (iPSCs) can be generated by overexpression of Oct4, Sox2 and Klf4 in murine fibroblasts. By conducting a microRNA (miRNA) library screen, we identified a set of miRNAs critically regulating iPSC formation. We revealed a new miRNA family (miR-130/301/721) as an important regulator of iPSC induction by targeting the homeobox transcription factor Meox2 (also known as Gax). Meox2-specific silencing mimicked the effects of this miRNA family on reprogramming. Mechanistically, miRNA-resistant Meox2 overexpression abrogated effects of miR-130/301/721 on reprogramming. In conclusion, the miRNA family miR-130/301/721 enhances iPSC generation via repression of Meox2.
引用
收藏
页码:1153 / 1159
页数:7
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